Thalidomide neuropathy in patients treated for metastatic prostate cancer.

We prospectively evaluated thalidomide-induced neuropathy using electrodiagnostic studies. Sixty-seven men with metastatic androgen-independent prostate cancer in an open-label trial of oral thalidomide underwent neurologic examinations and nerve conduction studies (NCS) prior to and at 3-month intervals during treatment. NCS included recording of sensory nerve action potentials (SNAPs) from median, radial, ulnar, and sural nerves. SNAP amplitudes for each nerve were expressed as the percentage of its baseline, and the mean of the four was termed the SNAP index. A 40% decline in the SNAP index was considered clinically significant. Thalidomide was discontinued in 55 patients for lack of therapeutic response. Of 67 patients initially enrolled, 24 remained on thalidomide for 3 months, 8 remained at 6 months, and 3 remained at 9 months. Six patients developed neuropathy. Clinical symptoms and a decline in the SNAP index occurred concurrently. Older age and cumulative dose were possible contributing factors. Neuropathy may thus be a common complication of thalidomide in older patients. The SNAP index can be used to monitor peripheral neuropathy, but not for early detection.

"Pseudo-conduction block" in a patient with vasculitic neuropathy.

A 63-year-old man presented with progressive asymmetric weakness and numbness in his hands of 2 weeks duration. Nerve conduction studies showed low amplitude motor evoked potentials of both median nerves. The right ulnar, left tibial and peroneal nerves had normal potentials on distal stimulation with markedly decreased amplitudes proximally, suggestive of "conduction block". Three weeks later, amplitudes were decreased throughout. The patient was diagnosed with vasculitis. The acute ischemic injury presumably resulted in axonal damage between the distal and proximal stimulation sites, with subsequent Wallerian degeneration.

Motor cortex excitability in stiff-person syndrome.

Muscle stiffness in stiff-person syndrome (SPS) is produced by continuous, involuntary firing of motor units that is thought to be caused by an autoimmune mediated dysfunction of GABA-ergic inhibitory neurones. We have postulated that the loss of GABA-ergic inputs from spinal interneurones alone is insufficient to produce tonic firing of motor neurones and that excessive supraspinal excitation could also play a role. To determine whether SPS is associated with dysfunction in supraspinal GABA-ergic neurones, we assessed the excitability of the motor cortex with transcranial magnetic stimulation (TMS) in seven SPS patients and seven age-matched healthy volunteers. SPS patients had normal central motor conduction times, normal thresholds for motor evoked potentials (MEPs) in leg muscles, and a normal MEP stimulus versus response recruitment curve with increasing TMS intensities in resting hand and leg muscles. Cortical silent periods were shortened in leg muscles. Intracortical inhibition and excitation were assessed while recording from the abductor pollicis brevis, using a paired pulse TMS paradigm with subthreshold conditioning stimuli. Patients had decreased inhibition and markedly increased facilitation at short intervals. Using paired suprathreshold TMS, patients exhibited increased facilitation at 20- and 40-ms intervals. These results point to a hyperexcitability of the motor cortex in SPS, which could be explained by impairment of supraspinal GABA-ergic neurones, leading to an impaired balance between inhibitory and excitatory intracortical circuitry.

Cutaneous silent periods in patients with Fabry disease.

We assessed the cutaneous silent period (CSP) in 24 patients with Fabry disease with small-fiber sensory neuropathy and 12 normal subjects to test the hypothesis that small-diameter afferents are responsible for producing the CSP. Sensory nerve conduction studies and quantitative sensory testing for cold and vibration detection thresholds were also measured. Overall, Fabry patients had impaired thermal, but not vibration, detection thresholds, with greatest impairment in the feet. In the upper extremity, CSP latencies, duration, and suppression of electromyographic activity (EMG) did not differ. In the lower extremity, patients had reduced suppression of EMG during the CSP compared to normal controls. CSP durations exhibited a bimodal distribution in patients, including a subset of seven patients with durations shorter than all controls. This subset had profound loss of thermal sensation in the feet, but this was also true of some patients who had normal CSPs. Patients with shortened CSPs had modestly elevated vibration thresholds and reduced sensory potentials in comparison to patients with normal CSPs. Reduced CSPs in Fabry patients are associated with, but not entirely explained by, the severity of small-fiber neuropathy as measured by quantitative sensory testing. The possibility that large-diameter fibers provide a minor contribution to producing the CSP should be considered.

Blink reflex recovery in facial weakness: an electrophysiologic study of adaptive changes.

OBJECTIVE: To study the electrophysiologic effects of unilateral facial weakness on the excitability of the neuronal circuitry underlying blink reflex, and to localize the site of changes in blink reflex excitability that occur after facial weakness. BACKGROUND: Eyelid kinematic studies suggest that adaptive modification of the blink reflex occurs after facial weakness. Such adaptations generally optimize eye closure. A report of blepharospasm following Bell's palsy suggests that dysfunctional adaptive changes can also occur. METHODS: Blink reflex recovery was evaluated with paired stimulation of the supraorbital nerve at different interstimulus intervals. Comparisons were made between normal control subjects and patients with Bell's palsy who either recovered facial strength or who had persistent weakness. RESULTS: Blink reflex recovery was enhanced in patients with residual weakness but not in patients who recovered facial strength. Facial muscles on weak and unaffected sides showed enhancement. In patients with residual weakness, earlier blink reflex recovery occurred when stimulating the supraorbital nerve on the weak side. Sensory thresholds were symmetric. CONCLUSION: Enhancement of blink reflex recovery is dependent on ongoing facial weakness. Faster recovery when stimulating the supraorbital nerve on the paretic side suggests that sensitization may be lateralized, and suggests a role for abnormal afferent input in maintaining sensitization. Interneurons in the blink reflex pathway are the best candidates for the locus of this plasticity.

Zoster myelitis: improvement with antiviral therapy in two cases.

This report describes two patients with acquired immunodeficiency syndrome (AIDS) and herpes zoster myelopathy. Patient one had a T-8 myelitis that preceded the onset of T-8-distribution zoster and was followed by cervical myelopathy. Antibody to varicella zoster virus (VZV) was present in the CSF. He never received steroids or other immunosuppressive drugs, and his condition improved dramatically after treatment with intravenous acyclovir. The second patient had a rapidly progressive myelitis with paralysis of both legs. Detection of VZV DNA and antibody to VZV in his CSF led to successful treatment with famciclovir despite discontinuation of dexamethasone and earlier treatment failure with acyclovir. These cases support the idea that VZV myelopathy in the immunosuppressed host is caused by virus invasion. CSF analysis for antiviral antibody and for VZV DNA by polymerase chain reaction are helpful in establishing the diagnosis. Aggressive antiviral therapy is advised.

Short communication: deletion 7q, trisomy 6 and 11 in a case of Merkel-cell carcinoma.

Chromosome analysis of a metastatic Merkel-cell carcinoma established as xenografted tumor line in nude mice was performed. The analyzed karyotypes showed a stable cytogenetic feature characterized by trisomy 6 and 11 and a partial deletion of the long arm of chromosome #7 with the breakpoint localized at q31.2.